The brothers investigate murders comitted by men under the spell of a siren, and a meet a doctor who takes a liking to Sam. Then the brothers fall under the spell themselves...

Just as Oliver is announcing to the LuthorCorp board of executives that Queen Industries has bought controlling interest in LuthorCorp a bomb detonates in the meeting room. Clark and Lana investigate the bombing and discover that the bomb was made with kryptonite. Lana also discovers that her suit not only gives her strength and speed, but absorbs kryptonite radiation as well. The bombmaker, Winslow Schott, a former Queen Industries employee now under the employ of Lex, plants another bomb on the roof of the Daily Planet. When Lana absorbs the kryptonite in this bomb to deactivate it, she becomes so irradiated that she and Clark can never again be near each other. Clark tracks Lex down, but Lana stops him from doing something he would regret, and Lex's mobile safe-house explodes. To keep from harming Clark, Lana leaves Smallville, again.

Blair comes up with a devious plan to take down her new teacher, Rachel. Chuck has no recollection of what happened to him when he wakes up in a hotel. Nate and Vanessa try to help Chuck fill in the missing pieces of his night. Meanwhile Dan and Serena try to keep their relationship together as Rufus and Lily grow even closer.

A former cancer researcher collapses in the middle of a cooking class, and the team are forced to reevaluate their own lives when they learn she gave up a promising career to seek personal happiness. Meanwhile, Thirteen suffers adverse reactions from the clinical trials, and Cuddy gives House a dose of his own medicine.

As Peyton begins to plan the wedding, Lucas attempts to put a cast together for his movie. Meanwhile, Haley is faced with a difficult decision, and Nathan gets great news.

Kyle hits the bar with Josh and Declan to drown his sorrows after breaking up with Amanda. Lori and Jessi bond over boys as Lori uses Jessi's apartment as a bolthole.

When Sheldon comes up with a plan to fix Penny's finances, it leads to Leonard coming face-to-face with her ex, Kurt.

After the battle between Pinehearst and Primatech, Pete, Claire, Matt, and Daphne try to live normal lives, while a powerless Hiro tries to teach Ando how to use his new special ability and become a superhero. However, Claire discovers Nathan's plan to track down those with abilities.